Time to the first occurrence of a component of the composite renal endpoint. [ Time Frame: Approximately 48 months. ] [ Designated as safety issue: Yes ]

Time to the first occurrence of a component of the composite renal endpoint: doubling of serum creatinine (confirmed by a 30-day serum creatinine) or the onset of end stage renal disease (estimated glomerular filtration rate (eGFR) less than 15 ml/min/1.73 m2 confirmed by a 90-day eGFR, receiving chronic dialysis, renal transplantation or renal death).

Original Primary Outcome Measures ICMJE (submitted: May 17, 2013)

Time to the first occurrence of a component of the composite renal endpoint. [ Time Frame: Approximately 48 months. ] [ Designated as safety issue: Yes ]

Time to the first occurrence of a component of the composite renal endpoint: doubling of serum creatinine (confirmed by a 30-day serum creatinine) or the onset of end stage renal disease (needing chronic dialysis or renal transplantation or renal death).

Time to first occurrence of a component of composite renal endpoint: confirmed doubling of serum creatinine or the onset of end stage renal disease for all randomized subjects (pooled). [ Time Frame: Approximately 48 months. ] [ Designated as safety issue: Yes ]

A Randomized, Multicountry, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Atrasentan on Renal Outcomes in Subjects With Type 2 Diabetes and Nephropathy SONAR: Study Of Diabetic Nephropathy With Atrasentan

Brief Summary

This study is being conducted to evaluate the effects of Atrasentan on Renal Outcomes in Subjects with Type 2 Diabetes and Nephropathy.

Detailed Description

The study objective is to evaluate the effect of atrasentan compared with placebo on time to doubling of serum creatinine or the onset of end stage renal disease (ESRD) in subjects with type 2 diabetes and nephropathy who are treated with the maximum tolerated labeled daily dose (MTLDD) of a Renin Angiotensin System (RAS) inhibitor. In addition, the study will assess the effects of atrasentan compared with placebo on cardiovascular morbidity and mortality, urine albumin excretion, changes in estimated glomerular filtration rate (eGFR), as well as on the impact on quality of life in subjects with type 2 diabetes and nephropathy.

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Recruiting

Estimated Enrollment ICMJE

4148

Estimated Completion Date

November 2018

Estimated Primary Completion Date

July 2018 (final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Subject has type 2 diabetes (including patients with latent autoimmune diabetes or insulin-treated patients without a history of diabetic ketoacidosis who also have a negative anti-glutamic acid decarboxylase test AND an elevated post-prandial serum C-peptide level) and has been treated with at least one anti-hyperglycemic medication and ACEi/or ARB (RAS inhibitor) for at least 4 weeks prior to the Screening S2 visit.

For entry into the Run-In Period the subject must satisfy the following criteria based on the Screening laboratory values:

Estimated glomerular filtration rate (eGFR) 25 to 75 mL/min/1.73 m2 and a urine albumin creatinine ratio (UACR) greater than or equal to 300 and less than 5,000 mg/g (greater than or equal to 34 mg/mmol and less than 565 mg/mmol);

Serum albumin greater than or equal to 2.5 g/dL (25 g/L);

Brain natriuretic peptide (BNP) less than or equal to 200 pg/mL (200 ng/L);

Systolic blood pressure (SBP) greater than or equal to 110 and less than or equal to 180 mmHg;

Serum Potassium greater than or equal to 3.5 mEq/L (3.5 mmol/L) and less than or equal to 6.0 mEq/L (6.0 mmol/L);

Subjects on a maximum tolerated labeled daily dose (MTLDD) of a RAS inhibitor for greater than or equal to 4 weeks and on a diuretic at the time of screening and who satisfy the above criteria may proceed to the last visit in Run-In Period (R6);

Subjects already on a MTLDD of a RAS inhibitor for greater than or equal to 4 weeks and not on a diuretic (unless medically contraindicated) at the time of Screening will start with a diuretic and proceed to Run-In for at least 2 weeks.

For entry into the Enrichment Period the subject must satisfy the following criteria based on the last visit of the Run-In Period:

RAS inhibitor at the MTLDD for the previous 4 weeks with no adjustments of the dose;

Subjects that were on a MTLDD RAS inhibitor and not on a diuretic (unless medically contraindicated) at the time of Screening must have been in Run-In for at least 2 weeks.

For entry into the Double-Blind Treatment Period, the subject must satisfy the following criteria based on the last visit of the Enrichment Period:

RAS inhibitor at the MTLDD for the previous 6 weeks during the Enrichment Period with no adjustments of the dose;

Diuretic at any dose unless medically contraindicated or clinically intolerable in the investigator's judgement (i.e., hypotension or hypokalemia);

Subject must not have a weight change greater than or equal to 3 kg from the beginning of Enrichment to the end of the Enrichment Period and absolute serum BNP greater than or equal to 300 pg/mL (300 ng/L) at the last Enrichment visit;

Subject must not have an increase in serum creatinine greater than 0.5 mg/dL and greater than 20% increase from the beginning of Enrichment to the end of the Enrichment Period.

Exclusion Criteria:

Subject has a history of severe peripheral edema or facial edema requiring diuretics unrelated to trauma or a history of myxedema in the prior 4 weeks to the initial Screening S1 visit.

Subject has a documented diagnosis of heart failure, previous hospitalization for heart failure or current or constellation of symptoms (dyspnea on exertion, pedal edema, orthopnea, paroxysmal nocturnal dyspnea) felt to be compatible with heart failure, that was not explained by other causes, and for which there was a change in medication or other management directed at heart failure.

Subject has known non-diabetic kidney disease (other than kidney stones).